Maintenance of long remission in adult T‐cell leukemia by Tax‐targeted vaccine: A hope for disease‐preventive therapy

• Published in: Cancer science Vol. 110; no. 3; pp. 849 - 857
• Main Authors: Kannagi, Mari, Hasegawa, Atsuhiko, Nagano, Yoshiko, Iino, Tadafumi, Okamura, Jun, Suehiro, Youko
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-03-2019; John Wiley and Sons Inc
• Subjects: Animals; Antigens; Apoptosis; Autografts; Cancer Vaccines - immunology; Chemokines; Chemotherapy; Cytokines; Cytotoxicity; Dendritic cells; Epitopes; Gene Products, tax - immunology; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; HTLV-I Infections - immunology; Human T-lymphotropic virus 1 - immunology; Humans; Immunoproliferative diseases; Immunotherapy; Infections; Kinases; Leukemia; Leukemia-Lymphoma, Adult T-Cell - immunology; Lymphocytes; Lymphocytes T; Lymphoma; Medical prognosis; Multiple myeloma; Patients; Peptides; Pilot Projects; Prophylaxis; Remission; Review; Stem cell transplantation; Stem cells; T-Lymphocytes, Cytotoxic - immunology; Tetanus; Vaccination; Vaccines; Viruses; Japan
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13948

Adult T‐cell leukemia/lymphoma (ATL) is an aggressive lymphoproliferative disease caused by human T‐cell leukemia virus type 1 (HTLV‐1). Multi‐agent chemotherapy can reduce ATL cells but frequently allows relapses within a short period of time. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) following chemotherapy is now a standard therapy for ATL in Japan as it can achieve long‐term remission in approximately one‐third of recipient ATL patients; however, it also has a risk of treatment‐related mortality. Allo‐HSCT often induces HTLV‐1 Tax‐specific cytotoxic T cells (CTL) as well as graft‐versus‐host (GVH) response in ATL patients. This observation led to development of a new therapeutic vaccine to activate Tax‐specific CTL, anticipating anti‐ATL effects without GVH response. The newly developed Tax‐DC vaccine consists of autologous dendritic cells pulsed with Tax peptides corresponding to CTL epitopes that have been identified in post‐allo‐HSCT ATL patients. In a pilot study of Tax‐DC therapy in three ATL patients after various initial therapies, two patients survived for more than 4 years after vaccination without severe adverse effects (UMIN000011423). The Tax‐DC vaccine is currently under phase I trial, showing a promising clinical outcome so far. These findings indicate the importance of patients’ own HTLV‐1‐specific T‐cell responses in maintaining remission and provide a new approach to anti‐ATL immunotherapy targeting Tax. Although Tax‐targeted vaccination is ineffective against Tax‐negative ATL cells, it can be a safe alternative maintenance therapy for Tax‐positive ATL and may be further applicable for treatment of indolent ATL or even prophylaxis of ATL development among HTLV‐1‐carriers.
Although adult T‐cell leukemia (ATL) is known to be resistant to chemotherapy, recent therapeutic approaches including hematopoietic stem cell transplantation, mogamulizumab and lenalidomide improved prognosis of ATL, all of which act through host immunity. More recently, a clinical study of novel anti‐ATL therapeutic vaccine targeting human T‐cell leukemia virus type 1 Tax was carried out in Japan for the first time with promising clinical outcomes. This review proposes a new concept of immunotherapy in ATL, by dissecting underlying mechanisms.